Tumor heterogeneity on FDG PET/CT and immunotherapy: An imaging biomarker for predicting treatment response in patients with metastatic melanoma

Y. Sanli, J. Leake, A. Odu, Y. Xi, R. M. Subramaniam

Research output: Contribution to journalArticle

Abstract

OBJECTIVE. The purpose of this study is to evaluate the ability of quantitative 18F-FDG PET parameters to predict outcomes of patients with malignant melanoma who have been treated with immune modulation therapy. MATERIALS AND METHODS. We retrospectively investigated 34 patients with malignant melanoma. Twenty-three patients received immunotherapy as first-line therapy, and 11 patients received it as second-line therapy. The maximum standardized uptake value (SUVmax), metabolic tumor volume, tumor lesion glycolysis, and intratumoral metabolic heterogeneity (as measured by the tumor heterogeneity [TH] index) were measured for the primary tumors and metastatic sites associated with up to five of the most FDG-avid lesions per patient. The TH index was calculated as the AUC value of a cumulative SUV volume histogram curve for all patients. The median follow-up was 29.5 months (range, 3-288 months). Outcome endpoints were progression-free survival and overall survival. Kaplan-Meier survival plots were used, and Cox regression analysis was performed for predictors of survival. RESULTS. A total of 101 lesions were analyzed. Five lesions were analyzed in 12 patients, four lesions in three patients, three lesions in three patients, two lesions in four patients, and one lesion in 12 patients. Of the 34 patients included in the study, 15 (44.1%) had disease progression and 11 (32.3%) had died by the time the last follow-up occurred. The mean (± SD) SUV max, peak SUV, metabolic tumor volume, tumor lesion glycolysis, and TH values for all lesions were 9.68 ± 6.6, 7.82 ± 5.83, 81.96 ± 146.87 mL, 543.65 ± 1022.92 g, and 5841.36 ± 1249.85, respectively. TH had a negative correlation with SUVmax, peak SUV, and tumor lesion glycolysis (p < 0.0001 for all). CONCLUSION. The TH index is significantly associated with overall survival in patients with metastatic melanoma treated with immune modulation therapy as first-line or second-line therapy.

Original languageEnglish (US)
Pages (from-to)1318-1326
Number of pages9
JournalAmerican Journal of Roentgenology
Volume212
Issue number6
DOIs
StatePublished - Jun 2019

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Immunotherapy
Melanoma
Biomarkers
Neoplasms
Therapeutics
Glycolysis
Survival
Tumor Burden
Fluorodeoxyglucose F18
Disease-Free Survival
Area Under Curve
Disease Progression
Regression Analysis

Keywords

  • F-FDG PET/CT
  • Immunotherapy
  • Metastatic melanoma
  • Tumor heterogeneity

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{8ca7257c5d3646e3a67d4fd16276ce5c,
title = "Tumor heterogeneity on FDG PET/CT and immunotherapy: An imaging biomarker for predicting treatment response in patients with metastatic melanoma",
abstract = "OBJECTIVE. The purpose of this study is to evaluate the ability of quantitative 18F-FDG PET parameters to predict outcomes of patients with malignant melanoma who have been treated with immune modulation therapy. MATERIALS AND METHODS. We retrospectively investigated 34 patients with malignant melanoma. Twenty-three patients received immunotherapy as first-line therapy, and 11 patients received it as second-line therapy. The maximum standardized uptake value (SUVmax), metabolic tumor volume, tumor lesion glycolysis, and intratumoral metabolic heterogeneity (as measured by the tumor heterogeneity [TH] index) were measured for the primary tumors and metastatic sites associated with up to five of the most FDG-avid lesions per patient. The TH index was calculated as the AUC value of a cumulative SUV volume histogram curve for all patients. The median follow-up was 29.5 months (range, 3-288 months). Outcome endpoints were progression-free survival and overall survival. Kaplan-Meier survival plots were used, and Cox regression analysis was performed for predictors of survival. RESULTS. A total of 101 lesions were analyzed. Five lesions were analyzed in 12 patients, four lesions in three patients, three lesions in three patients, two lesions in four patients, and one lesion in 12 patients. Of the 34 patients included in the study, 15 (44.1{\%}) had disease progression and 11 (32.3{\%}) had died by the time the last follow-up occurred. The mean (± SD) SUV max, peak SUV, metabolic tumor volume, tumor lesion glycolysis, and TH values for all lesions were 9.68 ± 6.6, 7.82 ± 5.83, 81.96 ± 146.87 mL, 543.65 ± 1022.92 g, and 5841.36 ± 1249.85, respectively. TH had a negative correlation with SUVmax, peak SUV, and tumor lesion glycolysis (p < 0.0001 for all). CONCLUSION. The TH index is significantly associated with overall survival in patients with metastatic melanoma treated with immune modulation therapy as first-line or second-line therapy.",
keywords = "F-FDG PET/CT, Immunotherapy, Metastatic melanoma, Tumor heterogeneity",
author = "Y. Sanli and J. Leake and A. Odu and Y. Xi and Subramaniam, {R. M.}",
year = "2019",
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doi = "10.2214/AJR.18.19796",
language = "English (US)",
volume = "212",
pages = "1318--1326",
journal = "American Journal of Roentgenology",
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TY - JOUR

T1 - Tumor heterogeneity on FDG PET/CT and immunotherapy

T2 - An imaging biomarker for predicting treatment response in patients with metastatic melanoma

AU - Sanli, Y.

AU - Leake, J.

AU - Odu, A.

AU - Xi, Y.

AU - Subramaniam, R. M.

PY - 2019/6

Y1 - 2019/6

N2 - OBJECTIVE. The purpose of this study is to evaluate the ability of quantitative 18F-FDG PET parameters to predict outcomes of patients with malignant melanoma who have been treated with immune modulation therapy. MATERIALS AND METHODS. We retrospectively investigated 34 patients with malignant melanoma. Twenty-three patients received immunotherapy as first-line therapy, and 11 patients received it as second-line therapy. The maximum standardized uptake value (SUVmax), metabolic tumor volume, tumor lesion glycolysis, and intratumoral metabolic heterogeneity (as measured by the tumor heterogeneity [TH] index) were measured for the primary tumors and metastatic sites associated with up to five of the most FDG-avid lesions per patient. The TH index was calculated as the AUC value of a cumulative SUV volume histogram curve for all patients. The median follow-up was 29.5 months (range, 3-288 months). Outcome endpoints were progression-free survival and overall survival. Kaplan-Meier survival plots were used, and Cox regression analysis was performed for predictors of survival. RESULTS. A total of 101 lesions were analyzed. Five lesions were analyzed in 12 patients, four lesions in three patients, three lesions in three patients, two lesions in four patients, and one lesion in 12 patients. Of the 34 patients included in the study, 15 (44.1%) had disease progression and 11 (32.3%) had died by the time the last follow-up occurred. The mean (± SD) SUV max, peak SUV, metabolic tumor volume, tumor lesion glycolysis, and TH values for all lesions were 9.68 ± 6.6, 7.82 ± 5.83, 81.96 ± 146.87 mL, 543.65 ± 1022.92 g, and 5841.36 ± 1249.85, respectively. TH had a negative correlation with SUVmax, peak SUV, and tumor lesion glycolysis (p < 0.0001 for all). CONCLUSION. The TH index is significantly associated with overall survival in patients with metastatic melanoma treated with immune modulation therapy as first-line or second-line therapy.

AB - OBJECTIVE. The purpose of this study is to evaluate the ability of quantitative 18F-FDG PET parameters to predict outcomes of patients with malignant melanoma who have been treated with immune modulation therapy. MATERIALS AND METHODS. We retrospectively investigated 34 patients with malignant melanoma. Twenty-three patients received immunotherapy as first-line therapy, and 11 patients received it as second-line therapy. The maximum standardized uptake value (SUVmax), metabolic tumor volume, tumor lesion glycolysis, and intratumoral metabolic heterogeneity (as measured by the tumor heterogeneity [TH] index) were measured for the primary tumors and metastatic sites associated with up to five of the most FDG-avid lesions per patient. The TH index was calculated as the AUC value of a cumulative SUV volume histogram curve for all patients. The median follow-up was 29.5 months (range, 3-288 months). Outcome endpoints were progression-free survival and overall survival. Kaplan-Meier survival plots were used, and Cox regression analysis was performed for predictors of survival. RESULTS. A total of 101 lesions were analyzed. Five lesions were analyzed in 12 patients, four lesions in three patients, three lesions in three patients, two lesions in four patients, and one lesion in 12 patients. Of the 34 patients included in the study, 15 (44.1%) had disease progression and 11 (32.3%) had died by the time the last follow-up occurred. The mean (± SD) SUV max, peak SUV, metabolic tumor volume, tumor lesion glycolysis, and TH values for all lesions were 9.68 ± 6.6, 7.82 ± 5.83, 81.96 ± 146.87 mL, 543.65 ± 1022.92 g, and 5841.36 ± 1249.85, respectively. TH had a negative correlation with SUVmax, peak SUV, and tumor lesion glycolysis (p < 0.0001 for all). CONCLUSION. The TH index is significantly associated with overall survival in patients with metastatic melanoma treated with immune modulation therapy as first-line or second-line therapy.

KW - F-FDG PET/CT

KW - Immunotherapy

KW - Metastatic melanoma

KW - Tumor heterogeneity

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